• 한국임상약학회지
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• 제24권1호
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• pp.1-8
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• 2014

Objective: Currently, rivaroxaban is widely used clinically for thromboprophylaxis after surgery. However, there are concerns on effectiveness and safety of rivaroxaban for its proper use. We aimed to evaluate the effectiveness and safety of rivaroxaban in orthopaedic patients after total hip replacement surgery in a large medical centre after the preferred formulary was switched from enoxaparin to rivaroxaban. Methods: The study was conducted on the patients who underwent hip arthroplasty surgery at the department of Orthopaedic Surgery at Seoul St. Mary's Hospital, South Korea. Electronic medical records were retrospectively reviewed to identify patients treated with rivaroxaban following total hip replacement between February 2011 and March 2012. Evaluation criteria included indications for use, dose, initiation and duration of therapy, drug interactions, adverse reactions, and status of health care reimbursement. The patients who were on enoxaparin were also reviewed as a reference. Results: We identified 57 patients who received rivaroxaban and 50 who received enoxaparin. All patients were prescribed the drugs for Korean Food and Drug Administration-approved indications. No thromboembolic or bleeding events were observed in either group. However, only 5.3% of rivaroxaban- treated patients had an appropriate length of prophylaxis and only 3.5% began rivaroxaban treatment at the recommended time. Surprisingly, 47.4% of rivaroxaban-treated patients received rivaroxaban despite being ineligible for reimbursement benefits. Conclusion: Rivaroxaban was generally well tolerated clinically. However, the duration of treatment, the time of initiation and patient eligibility for reimbursement require improvements, emphasising the need for education which indicates the area of pharmacists' involvement.

• 한국임상약학회지
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• 제26권3호
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• pp.195-200
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• 2016

Background: Venous thromboembolism (VTE) is a common and life-threating condition in cancer patients. Low molecular weight heparins (LMWH), such as dalteparin, are recommended in the treatment of VTE. Also, rivaroxaban, an orally administered direct factor Xa inhibitor, was approved for the treatment of VTE. It showed similar efficacy to standard therapy (LMWH or warfarin) and was associated with significantly lower rates of major bleedings. However, in the real world, bleeding has been reported to occur frequently in cancer patient receiving rivaroxaban. The goal of this research was to analyze bleeding risks between rivaroxaban and dalteparin for treatment of VTE in cancer patients. Methods: Medical records of oncology patients who were treated with rivaroxaban or dalteparin for VTE from July 2012 to June 2014 were retrospectively reviewed. Data collected were as follows: age, sex, weight, height, cancer types and stages, ECOG (eastern cooperative oncology group) PS (performance score), VTE types, concurrently used medications, study drug information (dose and duration of therapy), INR (international normalized ratio), PT (prothrombin time), and platelet counts. Bleeding was classified into major bleedings, clinically relevant non-major bleedings, and minor bleedings. Results: A total of 399 patients were included in the study. Of these patients, 246 were treated with rivaroxaban and 153 with dalteparin. Bleeding rates were significantly higher in the rivaroxaban group than in the dalteparin group (adjusted odds ratio (AOR) 2.09, 95% CI 1.22-3.60) after adjusting for confounders. In addition, rivaroxaban remained independently associated with 1.78-fold (95% CI 1.14-2.76) shorter time to bleeding compared to dalteparin after adjusting other factors known to be associated with poor outcomes. Conclusion: This study suggested that rivaroxaban was associated with an increased risk of bleedings in cancer patients.

• 한국임상약학회지
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• 제26권3호
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• pp.207-212
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• 2016

Objective: Prescription rate of dabigatran and rivaroxaban, which are the direct oral anticoagulants (DOAC), has increased. We have analyzed the prescription trend and medication use of dabigatran and rivaroxaban in patients with non-valvular atrial fibrillation (NVAF). Methods: It was retrospectively studied from September 2012 to April 2014 using the electronic medical records and the progress notes. Patients with NVAF (n=424) were evaluated on the medication use, prescribing preferences, adverse drug reactions (ADRs) and the availability of prescription reimbursement of dabigatran (n=210) and rivaroxaban (n=214). Results: Dabigatran was prescribed higher than rivaroxaban (23.3% versus 7.5%, p<0.001) in the neurology department, but rivaroxaban was prescribed higher compared to dabigatran in the cardiology department (87.4% versus 74.3%, p<0.001). Dabigatran was prescribed more than rivaroxaban in high risk patients with CHADS2 score ${\geq}3$ (44.3% versus 31.3%, p=0.006). Dabigatran patients seemed to have more ADRs than patients with rivaroxaban (25.2% versus 11.2%, p<0.001), but no serious thrombotic events and bleeding were found. Only 35.6% (n=151) were eligible for prescription reimbursement by the National Health Insurance (NHI). Bridging therapy (86, 31.5%) and direct-current cardioversion (57, 20.2%) were main reasons of ineligibility for reimbursement. Conclusion: Prescription preferences were present in choosing either dabigatran or rivaroxaban for patients with NVAF. Inpatient protocols and procedures considering patient-factors in NVAF need to be developed.

• 대한관절경학회지
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• 제16권2호
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• pp.121-127
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• 2012

목적: 관절경 수술을 시행 받은 환자의 항응고 요법이 응고능에 미치는 영향과 대표적 항응고 약물 사이에 차이가 있는지 알아보기 위하여 항응고 약물 중 두 종류를 선택하여 사용한 환자들의 혈액 응고 검사를 수술 전후에 시행하여 수술 전 후 및 두 약물 간에 차이가 나타나는지에 대해 알아보았다. 대상 및 방법: 관절경 수술을 시행한 47예의 슬관절 혹은 고관절 환자를 대상으로 하였으며 환자군을 무작위로 enoxaparin과 rivaroxaban을 사용한 두 그룹으로 나누어 수술 전 및 수술 후 5일째 응고 검사를 시행하여 수술 전후 및 두 약물간의 결과를 비교하였다. 결과: 수술 전 시행한 응고 검사에서는 두 그룹간의 유의한 차이가 없었으나(P>0.05) 수술 후 5일째 시행한 응고 검사에서는 prothrombin time-international normalized ratio (PT-INR), activated partial thromboplastin time (aPTT)에서 증가 소견을 보였고 특히 rivaroxaban 환자군의 수치가 증가한 것으로 나타났다(P<0.05). 결론: 관절경 수술의 약물을 통한 항응고 요법은 혈액 검사를 통한 결과에서 출혈 경향 면에서 안전한 범위에서 수술전과 비교하여 통계적으로 유의한 차이를 보였으나 rivaroxaban을 사용한 환자 군에서 응고능의 정상 범위를 넘어서는 환자가 있어 rivaroxaban의 사용에 주의를 요할 것으로 생각된다.

• Tuberculosis and Respiratory Diseases
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• 제76권3호
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• pp.127-130
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• 2014

The risk of dying from a pulmonary embolism (PE) is estimated to be about 30% if inotropic support is required and no cardiopulmonary arrest occurs. Fibrinolysis in massive PE is regarded as a life-saving intervention, unless there is a high risk of bleeding following the use of the fibrinolytic therapy. Rivaroxaban is an oral factor Xa inhibitor, however its anticoagulation effects before or after administration of fibrinolytics in massive PE are still unknown. Two patents were admitted: 61-year-old woman with repeated syncope, and a 73-year-old woman was admitted with dyspnea and poor oral intake. Systemic arterial hypotension with radiologic confirmation led to a diagnosis of massive PE in both patients. Rivaroxaban was administered before in one, and after firbrinolytic therapy in the other. One showed similar efficacy of rivaroxaban with currently used anticoagulants after successful fibrinolysis, and the other one without antecedent administration of the fibrinolytic agent showed unfavorable efficacy of rivaroxaban.

• 한국분말재료학회지
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• 제30권4호
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• pp.305-309
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• 2023

This study aims to prepare a colloidal silica-containing powder to enhance the solubility and dissolution rate of rivaroxaban using a self-nanoemulsifying drug delivery system (SNEDDS). We investigate the impact of colloidal silica on a nanoemulsion system for preparing powdered SNEDDS. The liquid SNEDDS comprises 30/20/50 (w/w/w) Peceol/Cremophor RH40/Tween 80, which results in the formation of the smallest droplets. Three powdered SNEDDS formulations are prepared by suspending the liquid SNEDDS formulation using colloidal silica and spray drying. The powdered SNEDDS prepared with liquid SNEDDS and colloidal silica at a ratio of 1/0.5 (w/w) exhibits the highest water solubility (0.94 ± 0.62 vs. 26.70 ± 1.81 ㎍/mL) and dissolution rate (38.4 ± 3.6 vs. 85.5 ± 3.4%, 45 min) when compared to the drug alone. Morphologically, the liquid SNEDDS is adsorbed onto colloidal silica and forms smaller particles. In conclusion, an SNEDDS containing rivaroxaban, prepared using colloidal silica, facilitates the creation of a nanoemulsion and enhances the water solubility of rivaroxaban. Accordingly, this technology holds significant potential for commercialization.

• 한국임상약학회지
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• 제32권1호
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• pp.37-46
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• 2022

Background: Non-valvular atrial fibrillation (NVAF) is associated with ischemic stroke risk in the aging population. Observational studies have indicated beneficial effects of direct-acting oral anticoagulant (DOAC) against ischemic stroke compared to warfarin. This study aimed to investigate ischemic stroke incidence and bleeding risk in patients on DOAC therapy. Methods: Using the database of Korean Health Insurance Review and Assessment-Aged Patient Sample 2015, we conducted a retrospective cohort study. Study subjects with NVAF diagnosis and prescribed anticoagulants were enrolled. Propensity score (PS) matching by age, sex, comorbidities, and medications were used. The clinical outcomes were major adverse cerebro-cardiovascular events (MACCEs, ischemic stroke/systemic embolism, myocardial infarction, cardiac death) and bleeding events. A cox proportional hazard model analysis was performed to compare the outcomes with hazard ratio (HR) and 95% confidence interval (CI). Results: Total 4,773 elderly patients with NVAF were initially included. Four PS-matched groups including rivaroxaban vs. warfarin-only (n=1,079), dabigatran vs. warfarin-only (n=721), rivaroxaban vs. dabigatran (n=721), and switchers of warfarin to rivaroxaban vs. warfarin-only (n=287) were analyzed. Every group showed statistically similar results of MACCEs and bleeding events, except for the group of rivaroxaban vs. dabigatran. Rivaroxaban users showed higher risks of bleeding events than dabigatran users (HR 2.25, 95% CI 1.01-4.99). Conclusion: In the elderly patients with NVAF, efficacy and safety outcomes among oral anticoagulants including DOACs and warfarin were similar, while rivaroxaban are more likely to have higher bleeding risks than dabigatran. Further research using large size sample is needed.

• Journal of Dental Anesthesia and Pain Medicine
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• 제17권2호
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• pp.143-147
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• 2017

The use of novel oral anticoagulants (NOACs) has increased in recent times in an effort to overcome the shortcomings of warfarin. They are being used primarily for the prevention of thrombosis caused by atrial fibrillation and offer the advantages of having fewer drug interactions than warfarin, no dietary restrictions, and no requirement for regular blood tests. Although there is reportedly less postoperative bleeding even if the drug is not discontinued during procedures that can cause local bleeding, such as dental procedures, no well-designed clinical studies have assessed postoperative bleeding associated with the use of these drugs. This article reports a case of a 74-year-old male patient who was taking rivaroxaban. The patient underwent a dental implant procedure after discontinuing rivaroxaban for one day and subsequently suffered delayed bleeding on postoperative day 6. Accordingly, this article also reports that the use of NOACs may also lead to delayed bleeding.

• Mass Spectrometry Letters
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• 제10권2호
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• pp.66-70
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• 2019

Rivaroxaban (RRN) is the first available active direct factor Xa inhibitor (anticoagulant) with oral administration. Due to its success in market, there have been efforts to develop various RRN formulations, and the development of good analytical methods for its in vivo evaluation is an essential prerequisite. Thus, here, a simple and efficient method to determine RRN in rat plasma using liquid-liquid extraction (LLE) and liquid chromatography and multiple reaction monitoring (LC-MRM) was presented. The use of ethyl acetate as the LLE solvent results appropriate extraction and purification of RRN and it also helps the significant reduction of rat plasma volume required for RRN quantitation. The developed method showed good analytical performance including specificity, linearity ($r^2{\geq}0.999$ within 0.5 - 500 ng/mL), sensitivity (the lower limit of quantitation at 0.5 ng/mL), accuracy (89.3 - 107.0%), precision (${\geq}12.7%$), and recovery (89.2 - 105.7%). Additionally, RRN in sample extracts showed good stability. Finally, the applicability of the validated method to the PK evaluation of RRN was confirmed after its oral administration to normal rats. The present method is the first analytical method employing LLE for the simple and efficient extraction and purification of RRN in rat plasma. Therefore, the present method can contribute to the development of new RRN formulations as well as to the monitoring of RRN in special clinical situations through its efficient determination in various samples with or without minor modification.

• 대한상부위장관⦁헬리코박터학회지
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• 제18권4호
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• pp.219-224
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• 2018

New oral anticoagulants (NOACs) are now widely used for the prevention and treatment of venous thrombosis, and for the prevention of stroke and systemic embolism in patients with atrial fibrillation. As compared with warfarin, NOACs have the advantage of rapid onset of action and less drug interaction. However, they carry a higher risk of gastrointestinal (GI) bleeding than warfarin. The risk of GI bleeding in patients using NOACs varies according to the type and dose of the drug. By contrast, apixaban and edoxaban are reported to carry similar risks as warfarin, and the risks with dabigatran and rivaroxaban are higher than that with warfarin. In patients using NOACs, old age, impaired renal function, impaired liver function, concurrent use of antiplatelet agents, and nonsteroidal anti-inflammatory drugs are considered major risk factors of GI bleeding, and gastroprotective agents such as histamine-2 receptor antagonist and proton pump inhibitor have preventive effects. To prevent GI bleeding associated with NOACs, the characteristics of each NOAC and the risk factors of bleeding should be recognized.